Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats.
OBJECTIVE
Recent findings suggest that bone marrow stem cells can differentiate into numerous cell types. This would provide a potentially unlimited source of isletlike cells for transplantation and a promising therapy for diabetes mellitus. Here, we studied the differentiation ability of adult bone marrow hematopoietic-rich stem cells to form glucose-regulating insulin-producing cells. Their ability to treat chemically induced diabetes in rats was then tested.


METHODS
Hematopoietic-rich stem cells were obtained from the long bones of rats and cultured in a serum-free medium containing 1% dimethyl sulfoxide for 3 days. The cells were cultured for 7 days in a glucose-rich medium supplemented with pancreatic extract. Thereafter, cultures were done in a medium (low concentration of glucose and 5% fetal bovine serum) supplemented with nicotinamide and exendin-4 for 7 more days.


RESULTS
At day 17 of culture, the cells formed isletlike clusters. These were distinctly stained crimson red by diphenylthiocarbazone and expressed insulin and endocrine-specific transcription genes. Insulin was secreted in a dose-response manner as a function of increasing glucose concentrations. When transplanted in the testes of diabetic rats, the differentiated cells could normalize blood glucose levels for 3 months in 80% of the treated rats. The therapeutic benefits were reversed after orchidectomy.


CONCLUSIONS
Hematopoietic-rich stem cells may include pancreatic progenitor cells capable of differentiating into functioning endocrine hormone-producing cells. This finding suggests a possible means of treating diabetes mellitus.
Gabr
Mahmoud M
MM
Departments of Biotechnology, Urology and Nephrology Center, Mansoura University, 35516, Mansoura, Egypt.
Sobh
Mohamed M
MM
Zakaria
Mahmoud M
MM
Refaie
Ayman F
AF
Ghoneim
Mohamed A
MA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006085:Graft Survival; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin